Nitric oxide (NO) is an important pleiotropic molecule mediating a wide range of physiological and pathophysiological processes. For example, it enhances activity of cyclooxygenase II (COX-II), an enzyme responsible for the synthesis of prostaglandins, which mediate inflammation, pain, and fever. See Liu, et al., Carcinogenesis, 2003, Vol. 24, No. 4, 637-642.
NO is produced from L-arginine and molecular oxygen by three distinct isoforms of nitric oxide synthase (NOS), i.e., neural NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Among the three isoforms, iNOS can be induced by endotoxins, cytokines (e.g., TNF-α), and certain transcriptional factors (e.g., NF-κB and AP1). It is the major target for preventing NO overproduction.